Abstract

FORMULATION AND EVALUATION OF CAPTOPRIL FLOATING TABLETS EMPLOYING A NEW MODIFIED STARCH – OPTIMIZATION BY 23 FACTORIAL DESIGN

Swathi G*, K. P. R. Chowdary and A. Muralidhar Rao.

Abstract

The objective of the present study is optimization of captopril floating tablet formulation by 23 factorial design. Floating tablets of captopril (100 mg) were formulated employing Cross linked starch-urea, a new modified starch (50 %) as matrix forming polymer, sodium bicarbonate as gas generating agent and beeswax and starch acetate as floating enhancers. Captopril is an ACE inhibitor and is widely prescribed for the treatment of hypertension and congestive heart failure. It has been reported, however, that the duration of antihypertensive action after a single oral dose of Captopril is only 6 – 8 h. Clinical use requires a daily dose of 30 – 60 mg to be taken 2 - 3 times a day. It is most stable at PH 1.2 and as the PH increases, it becomes unstable and undergoes a degradation reaction. Captopril floating tablets were formulated as per 23 factorial design. The three factors involved in the 23 factorial design are sodium bicarbonate (Factor A), beeswax (Factor B) and starch acetate (Factor C). The two levels of sodium bicarbonate (Factor A) are 10 and 20 %, the two levels of beeswax (Factor B) are 2 % and 5 % and the two levels of starch acetate (Factor C) are 5% and 10%. Eight captopril floating tablet formulations were prepared employing selected combinations of the levels of the three factors as per 23 factorial design. All the floating tablets prepared were evaluated for drug content, hardness, friability, disintegration time, floating lag time, floating time and drug release characteristics. Captopril floating tablets prepared as per 23 factorial design were non-disintegrating in water and aqueous acidic (pH 1.2) and alkaline (pH 7.4) fluids and were of good quality with regard to drug content, hardness, and friability and suitable for controlled release. The individual effects of sodium bicarbonate (Factor A) and starch acetate (Factor C) and their combined effect (AC) on the floating lag time were significant (P < 0.05).Whereas the individual effect of bees wax (Factor B) and all other combined effects of the three factors involved were not significant in influencing floating lag time of the tablets. Formulations Fab, Fac and Fabc exhibited excellent floating over 12-14 h with a floating lag time in the range 10-35 seconds. Higher levels (20 %) of sodium bicarbonate gave shorter floating lag time. Captopril release from the floating tablets prepared except formulation Fa was slow and spread over 12 h and dependent on the composition of the tablets. Drug release from formulation Fa was very rapid. Captopril release from the floating tablets was by non-fickian diffusion mechanism in all the cases except Fa. In the case of formulation Fa that gave rapid release of drug fickian diffusion was the drug release mechanism.

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